Objective To determine whether leptin, a protein that is associated with obesity in rodent models, has biological activity in a primate species. Leptin was identified, synthesized and administered to genetically obese mice and rats by investigators at other institutions during this report period. In these rodent models leptin has remarkable efficacy in reducing obesity and ameliorating the complications of obesity, such as insulin resistance. A very similar peptide has more recently been characterized in humans, but it is not known whether it has a similar biological activity or regulatory role to rodent leptin. To date, there have been no reports on the topic of leptin in nonhuman primates. We are just beginning a trial to evaluate the effects of human leptin (produced by E. coli) on energy metabolism in adult male rhesus monkeys. Food intake, body weight and composition, metabolic rate and physical activity, glucose tolerance and insulin sensitivity, and a panel of biocemical and hormonal markers will be assessed following periods of leptin administration in graded doses and of vehicle adiministration. Leptin levels in serum from rhesus monkeys of both sexes and various ages in a range of energy balance will also be surveyed by RIA using reagents developed for human studies and validated for rhesus macaques. Key words obesity, obesity-related morbidities, experimental pharmacology